1-247896121-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001001957.2(OR2W3):c.535C>T(p.Arg179Cys) variant causes a missense change. The variant allele was found at a frequency of 0.507 in 1,613,738 control chromosomes in the GnomAD database, including 213,360 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R179H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.43 ( 15702 hom., cov: 33)

Exomes 𝑓: 0.52 ( 197658 hom. )

Consequence

OR2W3
NM_001001957.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.59

Publications

29 publications found

Variant links:

Genes affected

OR2W3 (HGNC:15021): (olfactory receptor family 2 subfamily W member 3) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR2W3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.8534534E-5).

BP6

Variant 1-247896121-C-T is Benign according to our data. Variant chr1-247896121-C-T is described in ClinVar as Benign. ClinVar VariationId is 1582338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001957.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2W3	NM_001001957.2	MANE Select	c.535C>T	p.Arg179Cys	missense	Exon 1 of 1	NP_001001957.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2W3	ENST00000360358.3	TSL:6 MANE Select	c.535C>T	p.Arg179Cys	missense	Exon 1 of 1	ENSP00000353516.3

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65665

AN:

151958

Hom.:

15702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.444

GnomAD2 exomes

AF:

0.480

AC:

120564

AN:

251182

AF XY:

0.486

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.536

Gnomad OTH exome

AF:

0.495

GnomAD4 exome

AF:

0.515

AC:

753060

AN:

1461662

Hom.:

197658

Cov.:

AF XY:

0.513

AC XY:

373340

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.220

AC:

7349

AN:

33474

American (AMR)

AF:

0.355

AC:

15866

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

13365

AN:

26136

East Asian (EAS)

AF:

0.508

AC:

20161

AN:

39700

South Asian (SAS)

AF:

0.419

AC:

36174

AN:

86254

European-Finnish (FIN)

AF:

0.573

AC:

30620

AN:

53416

Middle Eastern (MID)

AF:

0.441

AC:

2545

AN:

5766

European-Non Finnish (NFE)

AF:

0.537

AC:

596807

AN:

1111802

Other (OTH)

AF:

0.500

AC:

30173

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

21336

42673

64009

85346

106682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16820

33640

50460

67280

84100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.432

AC:

65672

AN:

152076

Hom.:

15702

Cov.:

AF XY:

0.431

AC XY:

32079

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.225

AC:

9334

AN:

41508

American (AMR)

AF:

0.381

AC:

5825

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1769

AN:

3468

East Asian (EAS)

AF:

0.560

AC:

2873

AN:

5134

South Asian (SAS)

AF:

0.422

AC:

2035

AN:

4820

European-Finnish (FIN)

AF:

0.572

AC:

6053

AN:

10578

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36230

AN:

67968

Other (OTH)

AF:

0.445

AC:

940

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1793

3586

5378

7171

8964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.503

Hom.:

88638

Bravo

AF:

0.411

TwinsUK

AF:

0.545

AC:

2021

ALSPAC

AF:

0.540

AC:

2081

ESP6500AA

AF:

0.231

AC:

1016

ESP6500EA

AF:

0.532

AC:

4576

ExAC

AF:

0.477

AC:

57943

Asia WGS

AF:

0.482

AC:

1678

AN:

3478

EpiCase

AF:

0.538

EpiControl

AF:

0.531

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.69

MetaRNN

Benign

0.000039

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-4.2

PhyloP100

4.6

PrimateAI

Benign

0.39

PROVEAN

Benign

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.066

ClinPred

0.018

GERP RS

4.2

Varity_R

0.048

gMVP

0.12

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over